ArticleRetrovirology2004
Modulating HIV-1 replication by RNA interference directed against human transcription elongation factor SPT5.
Article in Retrovirology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 48 citations in OpenAlex.
- CDK9 and SPT5 proteins are specifically required for expression of herpes simplex virus 1 replication-dependent late genes.The Journal of biological chemistry · 2017Article
- The therapeutic landscape of HIV-1 via genome editing.AIDS research and therapy · 2017Review
- RNA interference approaches for treatment of HIV-1 infection.Genome medicine · 2015Article
- siRNA Genome Screening Approaches to Therapeutic Drug Repositioning.Pharmaceuticals (Basel, Switzerland) · 2013Article
- The Spt4-Spt5 complex: a multi-faceted regulator of transcription elongation.Biochimica et biophysica acta · 2013Review
- Mechanisms of HIV Transcriptional Regulation and Their Contribution to Latency.Molecular biology international · 2012Article
- Celastrol inhibits Tat-mediated human immunodeficiency virus (HIV) transcription and replication.Journal of molecular biology · 2011Article
- RNA interference-based therapeutics for human immunodeficiency virus HIV-1 treatment: synthetic siRNA or vector-based shRNA?Expert opinion on biological therapy · 2010Review
- Repression of RNA polymerase II elongation in vivo is critically dependent on the C-terminus of Spt5.PloS one · 2009Article
- Toward a durable anti-HIV gene therapy based on RNA interference.Annals of the New York Academy of Sciences · 2009Review
- Tat-SF1 is not required for Tat transactivation but does regulate the relative levels of unspliced and spliced HIV-1 RNAs.PloS one · 2009Article
- Nucleic acids-based therapeutics in the battle against pathogenic viruses.Handbook of experimental pharmacology · 2009Review
- Genetic and biochemical analysis of yeast and human cap trimethylguanosine synthase: functional overlap of 2,2,7-trimethylguanosine caps, small nuclear ribonucleoprotein components, pre-mRNA splicing factors, and RNA decay pathways.The Journal of biological chemistry · 2008Article
- Analysis of factor interactions with RNA polymerase II elongation complexes using a new electrophoretic mobility shift assay.Nucleic acids research · 2008Article
- RNA interference against viruses: strike and counterstrike.Nature biotechnology · 2007Review
- Therapeutic potential of RNA interference against cellular targets of HIV infection.Molecular biotechnology · 2007Review
- siRNAs targeting terminal sequences of the SARS-associated coronavirus membrane gene inhibit M protein expression through degradation of M mRNA.Journal of virological methods · 2007Article
- Coxsackievirus B3 and adenovirus infections of cardiac cells are efficiently inhibited by vector-mediated RNA interference targeting their common receptor.Gene therapy · 2007Article
- Small interfering RNAs against the TAR RNA binding protein, TRBP, a Dicer cofactor, inhibit human immunodeficiency virus type 1 long terminal repeat expression and viral production.Journal of virology · 2007Article
- RNAi therapy for HIV infection: principles and practicalities.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2007Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundSeveral cellular positive and negative elongation factors are involved in regulating RNA polymerase II processivity during transcription elongation in human cells. In recruiting several of these regulatory factors to the 5' long terminal repeat (LTR) promoter during transcription elongation, HIV-1 modulates replication of its genome in a process mediated by the virus-encoded transactivator Tat. One particular cellular regulatory factor, DSIF subunit human SPT5 (hSpt5), has been implicated in both positively and negatively regulating transcriptional elongation but its role in Tat transactivation in vivo and in HIV-1 replication has not been completely elucidated.
resultsTo understand the in vivo function of hSpt5 and define its role in Tat transactivation and HIV-1 replication, we used RNA interference (RNAi) to specifically knockdown hSpt5 expression by degrading hSpt5 mRNA. Short-interfering RNA (siRNA) designed to target hSpt5 for RNAi successfully resulted in knockdown of both hSpt5 mRNA and protein levels, and did not significantly affect cell viability. In contrast to hSpt5 knockdown, siRNA-mediated silencing of human mRNA capping enzyme, a functionally important hSpt5-interacting cellular protein, was lethal and showed a significant increase in cell death over the course of the knockdown experiment. In addition, hSpt5 knockdown led to significant decreases in Tat transactivation and inhibited HIV-1 replication, indicating that hSpt5 was required for mediating Tat transactivation and HIV-1 replication.
conclusionsThe findings presented here showed that hSpt5 is a bona fide positive regulator of Tat transactivation and HIV-1 replication in vivo. These results also suggest that hSpt5 function in transcription regulation and mRNA capping is essential for a subset of cellular and viral genes and may not be required for global gene expression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.